The majority of drugs in clinical use today are given either by injection or oral administration. Injections generally provide a fast, direct route to the bloodstream, whereas oral administration subjects the pharmaceutical agent to hepatic metabolism. Hepatic metabolism degrades the effectiveness of the pharmaceutical agents sometimes as much as 90% in some cases. The liver detoxifies drug molecules to a significant extent. As a result, a significant quantity may never reach the rest of the body due to the liver's detoxifying of the drug agent. Despite this drawback, oral administration still is the most preferred way of giving pharmaceutical drugs due to the ease of administration and the avoidance for the invasive techniques, such as injections.
Another, less common method of administration is by the use of ultrasonic vibration. An agent or drug may be driven through the skin, hair follicles, and sweat glands by the application of physical vibrations in the spectrum of KiloHertz to MegaHertz. Traditionally, there has been a great degree of variation in efficiency and modes of transfer.
There are problems associated with delivering drugs by ultrasound. For example, one obstacle is delivering an agent or drug past the skin and into the circulation where it can produce its desired effect.
The human, adult skin structure can be broken down into three layers. The stratum corneum, which is part of the epidermal layer, is the first layer of skin defense against the exterior environment. The stratum corneum is capable of absorbing superficial trauma while still maintaining adequate protection against loss of water and invasion of microorganisms and other substances. The intercellular space of the stratum corneum is approximately 30% by volume and has lipids contained within which form transport barriers.
The second layer of the epidermal layer consists of epidermal cells bound together by tight junctions into a matrix. Between the junctions lie lipid filled extracellular spaces containing a host of cellular lymphocytic factors enzymes and other antimicrobial agents. The epidermal layer is the body's prime protective barrier. Its basal cells provide metabolic and additional water barrier functions. The epidermal barrier provides a formidable defense structure even in the absence of the stratum corneum, especially to water soluble agents that do not possess a lipid extracellular phase.
The innermost layer is the dermal layer. The dermal layer consists of basil germ cells positioned upon a basil membrane. Below the basil membrane are the majority of the capillary loops that comprise the terminal states of the microcirculation tree. Penetrating all three skin layers are numerous hair follicles in various growth states. The hair follicle growth stage correlates with the death of the follicle.
WO094/08655 describes an ultrasonic transducer assembly comprising a stimulus transducer and a second transducer. The stimulus transducer creates an ultrasonic wave in the skin which causes microscopic openings through which the second transducer drives the agent through the openings. The stimuli transducer provides a first frequency from about five KiloHertz (KHz) to one MegaHertz (MHz) range for a predetermined period of time while the second transducer provides a variable frequency ultrasonic pump impulses in the MHz range. The device requires two different types of transducers and for optimal performance requires the stimulus and second transducer to be placed at an angle to each other.
There remains a need for cost-effective, improved sonophoretic systems that can deliver an agent or drug to an individual in a controlled manner.